FLEMINGTON, N.J.—Arno Therapeutics Inc., a clinical-stage biopharmaceutical company primarily focused on the development of therapeutics for cancer and other life-threatening diseases, has announced promising data supporting the ongoing clinical development program for lead compound onapristone—and a related companion diagnostic (CDx) effort—presenting said data at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting held May 29 to June 2 in Chicago.

“Results from our Phase 1 study in women with progesterone (PR) positive tumors have been immensely informative and critical to the advancement of our onapristone clinical development program. In addition to demonstrating clinical benefit in a group of heavily pretreated patients, the study demonstrated that Arno’s highly purified onapristone extended-release formulation has a very manageable safety profile, providing the recommended dose for the Phase 2 study currently underway,” according to Dr. Alex Zukiwski, CEO of Arno. “Additionally, results from the first portion of our Phase 1/2 study in men with advanced castration-resistant prostate cancer (CRPC) confirm the very acceptable safety profile of onapristone. We look forward to sharing details of these two studies and providing an update on our ongoing Phase 2 trial in women with recurrent or metastatic endometrioid cancer that expresses the APR [activated progesterone receptor].”

“Over the next 12 months, we plan to continue advancing both ongoing trials. We continue to screen and enroll patients in the ongoing Phase 2 study of women with recurrent or metastatic endometrioid cancer that expresses the APR,” Zukiwski tells DDNews. “The study is currently recruiting patients in France, and we plan to open sites in the U.S. later this year. The Phase 2 study focuses on the target indication of the onapristone development program, and will include up to 29 patients with recurrent or metastatic endometrioid tumors that have been shown to express the APR—i.e., tumors that are APR-positive—and who have received no more than one prior chemotherapy and no prior hormone therapy.

“The study utilizes a Simon two-stage design, meaning it will expand to additional patients once predetermined signals of efficacy are satisfied in the first stage. The first stage includes 10 patients; if two or more of these 10 patients respond, the study will recruit an additional 19 patients (stage 2) to confirm antitumor activity. If enrollment continues as planned, we hope to have signals of efficacy in the initial 10 patients later this year, in Q4 2015.”

Zukiwski continues, “Also presented at ASCO were results from the dose-escalation portion (21 patients) of our ongoing Phase 1/2 clinical trial in men with advanced CRPC whose tumors have progressed on treatment with abiraterone or enzalutamide, which is taking place at the Royal Marsden Hospital in the U.K.; these results confirm the very acceptable safety profile of oral, single-agent extended-release tablet formulation of onapristone. Given these results and that abiraterone is standard of care for CRPC, we will soon be starting an abiraterone plus onapristone combination program as part of the study. This will allow us to determine the RP2D of onapristone in combination with abiraterone and determine the activity of onapristone-abiraterone combination therapy and single agent onapristone in men with CRPC. We plan to begin screening and enrolling patients for this part of the study in the ensuing months.

“Finally, for both indications, we are developing and evaluating a companion diagnostic to detect APR to identify those patients more likely to respond to onapristone.”

One of the company’s recent studies explored in part the role of APR as a predictive immunohistochemical biomarker. APR analysis was performed on archival tumor tissue for each patient. Of 11 PR-positive endometrial tumors, six were APR-positive; of eight PR-positive breast cancer tumors, three were APR-positive; of five ovarian cancer tumors, one was APR-positive. To date, the diagnostic assay for APR has been optimized for endometrioid cancer and validation in additional tumor types is currently ongoing.

Onapristone is an oral, anti-progestin hormone blocker that has been shown in previous Phase 2 clinical trials (not sponsored by Arno) to exhibit considerable antitumor activity in patients with breast cancer. In preclinical testing, onapristone has been shown to block the activation of PR, which is believed to be a mechanism that inhibits the growth of APR-driven breast, endometrial and other gynecological tumors. APR has the potential to function as a biomarker of anti-progestin activity, as detected by a companion diagnostic currently under development with Arno’s partner, Leica Biosystems.